Enhancing Bond Strength Of Medical Devices

ABSTRACT

Components of medical devices include polyethylene-poly(ethylene oxide) amphiphilic graft copolymers (PE-g-PEO) in their base polymer formulations. The base polymeric formulations comprise at least a polymer or co-polymer of ethylene. These components are suitable for solvent-bonding with other components and enhance bond strength of the medical devices.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No.62/399,740, filed Sep. 26, 2016, the entire disclosure of which ishereby incorporated by reference herein.

TECHNICAL FIELD

Principles and embodiments of the present invention relate generally tomedical devices including polyethylene-poly(ethylene oxide) amphiphilicgraft copolymers (PE-g-PEO) in their base polymer formulations.Specifically, including PE-g-PEO in formulations for ethylene- and/orpropylene-containing polyolefin or thermoplastic elastomer (TPE) tubingenhances bonding strength between the tubing and connectors, where theconnectors are made of different materials compared to the tubing.

BACKGROUND

Medical tubing made from polyolefin (e.g., ethylene-orpropylene-containing) or thermoplastic elastomer (TPE) materials areused in, for example, infusion sets for delivery of intravenous (IV)fluids. Connectors are bonded to the tubing, thereby forming medicaldevices, which may be used alone or in conjunction with other medicaldevices to, for example, deliver fluids.

Solvent bonding is a technique used for joining molded plastic parts ofmedical devices. During the bonding process, the solvent dissolves thesurface of two mating parts and allows the material to flow together.Once the solvent evaporates, the result is a material-to-material bond.Many parts of medical devices made from plastics can be solvent-bondedin an application where ultrasonic bonding does not work. For dissimilarmaterials, however, solvent bonding does not typically achieve asatisfactory bonding. Namely, due to hydrophobicity and low surfaceenergy, the polyolefins and thermoplastic elastomers (TPEs) demonstratepoor interaction and solvent bonding with connector materials that aretypically made from poly(methyl methacrylate) (PMMA), styrene maleicanhydride (SMA), polycarbonate (PC), and methylmethacrylate-acrylonitrile-butadiene-styrene (MABS). For certainapplications such as an infusion kit with polyethylene orpolyethylene-containing-TPE tubing connected with a PMMA or SMA or PC orMABS connector, bonding performance between polyethylene or TPE and theconnector has not yet been acceptable. Solvents suitable for solventbonding processes include those solvents that can partially liquefyplastic along the joint and allow the joint to solidify causing apermanent chemical bonding. It is similar in end result to heat bondingmetal or thermoplastic. Bonded joints have an advantage over otheradhesives in that there is no third material creating the joint. Jointsare also airtight when created properly. Solvent bonding provides anadditional advantage in that it more readily integrates into rapidautomated assembly processes compared to more conventional adhesives,with a frequent cost advantage as well. Solvents suitable for solventbonding parts of medical devices are required to be non-flammable, notcarcinogenic, and not cause mechanical stress on the parts, an exampleof which is cyclohexanone.

Attempts have been made to improve bond strength. For example, U.S. Pat.No. No. 6,613,187 uses a cement composition comprising cyclicolefin-containing polymer and a solvent for solvent-bonding first andsecond polymeric materials. WO01/18112 also discloses a cementcomposition that is cyclic olefin containing polymer-based cementcomposition or bridged polycyclic hydrocarbon containing polymer-based.In addition, WO01/18112 discloses medical products that may besolvent-bonded, the products comprising homopolymers and/or copolymersof cyclic olefin containing polymers and bridged polycyclic hydrocarboncontaining polymers (collectively sometimes referred to as “COCs”). U.S.Pat. No. 6,649,681 uses a solvent-based adhesive to bond polymericfittings to components of articles used in medical applications. U.S.Pat. No. 6,673,192 uses cyanoacrylate adhesives activated with certainmulti-amine compounds to bond polyolefin substrates.

There is a continuing need to improve bond strength of medical devices.In particular, there is a need to improve bond strength of medicaldevices when bonding is done by a solvent, which is not flammable, notcarcinogenic, and does not cause mechanical stress of the parts. Due tothese solvent requirements, finding materials for components of medicaldevices that are suitable for solvent-bonding is an on-going challenge.

SUMMARY

Provided are components of medical devices, e.g., tubing, which exhibitenhanced bonding to other components, e.g., connectors.

Various embodiments are listed below. It will be understood that theembodiments listed below may be combined not only as listed below, butin other suitable combinations in accordance with the scope of thedisclosure.

A first aspect is a tubing for a medical device formed from a blendcomprising: a base polymeric formulation comprising at least a polymeror co-polymer of ethylene or propylene and excluding free poly(ethyleneoxide); and an additive comprising a polyethylene-poly(ethylene oxide)amphiphilic graft copolymer (PE-g-PEO); the PE-g-PEO being present inthe blend in an amount in the range of about 0.01 to about 5.0% byweight of the blend.

The base polymeric formulation may comprise polyethylene, polypropylene,a polyethylene-polypropylene co-polymer, a polyethylene- and/orpolypropylene-containing thermoplastic elastomer (TPE), or combinationsthereof. The base polymeric formulation may comprise a co-polymer ofpolyethylene and polypropylene. The polyethylene-and/orpolypropylene-containing thermoplastic elastomer (TPE) may comprise atleast 60 mol % total polyethylene and/or polypropylene. The PE-g-PEO maybe a product of ethylene oxide ring-opening polymerization of anethylene vinyl acetate copolymer having from 10 to 40 weight percent ofvinyl acetate. In one or more embodiments, the PE-g-PEO is effective toenhance bonding of the tubing to a connector.

Another aspect is a medical device comprising: a tubing comprising apolymeric blend comprising a base polymeric formulation comprising atleast a polymer or co-polymer of ethylene or propylene and excludingfree poly(ethylene oxide), and an additive comprising apolyethylene-poly(ethylene oxide) amphiphilic graft copolymer(PE-g-PEO), wherein the PE-g-PEO is present in the blend in an amount inthe range of about 0.01 to about 5.0% by weight of the blend; and aconnector bonded to the tubing, wherein the PE-g-PEO is effective toenhance bonding of the tubing to a connector.

The base polymeric formulation may comprise polyethylene, polypropylene,a polyethylene-polypropylene co-polymer, a polyethylene- and/orpolypropylene-containing thermoplastic elastomer (TPE), or combinationsthereof. The base polymeric formulation may comprise a co-polymer ofpolyethylene and polypropylene. The polyethylene-and/orpolypropylene-containing thermoplastic elastomer (TPE) may comprise atleast 60 mol % total polyethylene and/or polypropylene. The PE-g-PEO maybe a product of ethylene oxide ring-opening polymerization of anethylene vinyl acetate copolymer having from 10 to 40 weight percent ofvinyl acetate. The connector may comprise a polar material. The polarmaterial may be selected from the group consisting of: poly(methylmethacrylate) (PMMA), styrene maleic anhydride (SMA), polycarbonate(PC), and methyl methacrylate-acrylonitrile-butadiene-styrene (MABS).The connector may be solvent-bonded to the tubing.

An additional aspect is a method of making a medical device comprising:obtaining a polyethylene-poly(ethylene oxide) amphiphilic graftcopolymer (PE-g-PEO); combining the PE-g-PEO with a base polymericformulation comprising at least a polymer or co-polymer of ethylene orpropylene and excluding free poly(ethylene oxide) to form a blend, thePE-g-PEO being present in the blend in an amount in the range of about0.01 to about 5.0% by weight of the blend; forming a tubing from theblend; bonding the tubing to a connector in the presence of a solvent toform the medical device.

Ethylene oxide ring-opening polymerization of an ethylene vinyl acetatecopolymer having from 10 to 40 weight percent of vinyl acetate may beused to form the PE-g-PEO.

Various embodiments are listed below. It will be understood that theembodiments listed below may be combined not only as listed below, butin other suitable combinations in accordance with the scope of theinvention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a plan view illustrating a portion of an exemplary intravenous(IV) infusion kit comprising tubing, an IV injection port, andconnection;

FIG. 2 is a graph of bond strength (N) versus PE-g-PEO concentration(weight %) for Comparative Example 1 (0%) and Example 2 (0.5 wt.-%,1.0%, 2.5%, and 5.0% by weight of the formulation), which usedPE-760-g-PEO-8 as the additive to the base formulation;

FIG. 3 is a graph of bond strength (N) versus PE-g-PEO concentration(weight %) for Comparative Example 1 (0%) and Example 3 (0.5 wt.-%,1.0%, 2.5%, and 5.0% by weight of the formulation), which usedPE-760-g-PEO-4 as the additive to the base formulation;

FIG. 4 provides a graph of bond strength (N) towards PMMA material “B”versus PEO chain length (“z”) for Comparative Example 1 (PE only) andExample 4 (“z”: 0.25, 1, 4, and 8), which used PE-760-g-PEO-z as theadditive to the base formulation;

FIG. 5 provides a graph of bond strength (N) towards SMA material “B”versus PEO chain length (“z”) for Comparative Example 1 (PE only) andExample 4 (“z”: 0.25, 1, 4, and 8), which used PE-760-g-PEO-z as theadditive to the base formulation;

FIG. 6 provides a graph of bond strength (N) towards PC material “B”versus PEO chain length (“z”) for Comparative Example 1 (PE only) andExample 4 (“z”: 0.25, 1, 4, and 8), which used PE-760-g-PEO-z as theadditive to the base formulation;

FIG. 7 provides a graph of bond strength (N) towards MABS material “B”versus PEO chain length (“z”) for Comparative Example 1 (PE only) andExample 4 (“z”: 0.25, 1, 4, and 8), which used PE-760-g-PEO-z as theadditive to the base formulation;

FIG. 8 provides a graph of bond strength (N) towards PMMA material “B”versus PE segment length for Comparative Example 1 (PE only) and Example5 (“PE1-g-PEO”, where “XXX” & “z” are 360 & 7, respectively; “PE2-g-PEO,where “XXX” & “z” are 460 & 4, respectively; and “PE3-g-PEO”, where“XXX” & “z” are 660 & 3.5, respectively), which used PE-XXX-g-PEO-z asthe additive to the base formulation;

FIG. 9 provides a graph of bond strength (N) towards SMA material “B”versus PE segment length for Comparative Example 1 (PE only) and Example5 (“PE1-g-PEO”, where “XXX” & “z” are 360 & 7, respectively; “PE2-g-PEO,where “XXX” & “z” are 460 & 4, respectively; and “PE3-g-PEO”, where“XXX” & “z” are 660 & 3.5, respectively), which used PE-XXX-g-PEO-z asthe additive to the base formulation;

FIG. 10 provides a graph of bond strength (N) towards PC material “B”versus PE segment length for Comparative Example 1 (PE only) and Example5 (“PE1-g-PEO”, where “XXX” & “z” are 360 & 7, respectively; “PE2-g-PEO,where “XXX” & “z” are 460 & 4, respectively; and “PE3-g-PEO”, where“XXX” & “z” are 660 & 3.5, respectively), which used PE-XXX-g-PEO-z asthe additive to the base formulation; and

FIG. 11 provides a graph of bond strength (N) towards PC material “B”versus PE segment length for Comparative Example 1 (PE only) and Example5 (“PE1-g-PEO”, where “XXX” & “z” are 360 & 7, respectively; “PE2-g-PEO,where “XXX” & “z” are 460 & 4, respectively; and “PE3-g-PEO”, where“XXX” & “z” are 660 & 3.5, respectively), which used PE-XXX-g-PEO-z asthe additive to the base formulation;

FIG. 12 is a graph of bond strength (N) versus PE-g-PEO concentration inbase formulation (weight %) for Example 6 (0%, 0.5%, 1.0%, 2.5%, and5.0% by weight of the formulation), which used PE-760-g-PEO-7 as theadditive to a TPE base formulation;

FIG. 13 is a graph of bond strength (N) versus PE-g-PEO concentration inbase formulation (weight %) for Example 7 (0%, 0.5%, 1.0%, 2.5%, and5.0% by weight of the formulation), which used PE-760-g-PEO-4 as theadditive to the TPE base formulation; and

FIG. 14 is a graph of bond strength (N) versus PE concentration in anexemplary TPE base formulation, which used 0.5 wt.-% of PE-760-g-PEO-4as the additive in the base formulation.

DETAILED DESCRIPTION

Before describing several exemplary embodiments of the invention, it isto be understood that the invention is not limited to the details ofconstruction or process steps set forth in the following description.The invention is capable of other embodiments and of being practiced orbeing carried out in various ways.

The following terms shall have, for the purposes of this application,the respective meanings set forth below.

A base polymeric formulation is a material from which a medical devicemay be made. Preferably, the base polymeric formulations utilized inconjunction with the polyethylene-poly(ethylene oxide) amphiphilic graftcopolymers (PE-g-PEOs) disclosed herein comprise at least a polymer orco-polymer of ethylene. Exemplary desirable base polymeric formulationsinclude but are not limited to polyethylene, systems such as but notlimited to linear low density polyethylene (LLDPE),polyethylene-polypropylene co-polymers, and/or polyethylene-containingthermoplastic elastomers (TPEs). The base formulation may furtherinclude other ingredients, independently selected from one or more ofthe following: reinforcing and non-reinforcing fillers, plasticizers,antioxidants, stabilizers, processing oil, extender oils, lubricants,antiblocking, antistatic agents, waxes, foaming agents, pigments, flameretardants and other processing aids known in the compounding art.Fillers and extenders which can be utilized include conventionalinorganics such as calcium carbonate, clays, silica, talc, titaniumdioxide, carbon black, and the like. The processing oils generally areparaffinic, naphthenic or aromatic oils derived from petroleumfractions. The oils are selected from those ordinarily used inconjunction with the specific plastics or rubbers present in theformulation.

Reference to polyethylene-poly(ethylene oxide) amphiphilic graftcopolymers (PE-g-PEO) means that a graft copolymer is formed from anethylene-vinyl acetate containing monomer or prepolymer andpoly(ethylene oxide), resulting in a polyethylene backbone and PEO sidechains. The ethylene-vinyl acetate containing monomer or prepolymer mayprovide a desired functionality or reactivity to accept side chains, andthey may have a polyethylene backbone with pendant groups suitable toincorporate PEO.

Reference to “free poly(ethylene oxide)” means poly(ethylene oxide) thatis not part of the polyethylene-poly(ethylene oxide) amphiphilic graftcopolymers.

As used herein the term “connector” is understood to include anystructure that is part of an intravenous device that is capable ofmaking a connection with a secondary intravenous device. Non-limitingexamples of connectors in accordance with the present invention includeneedleless connectors, male Luer connectors, female Luer connectors,side port valves, y-port valves, port valves, and other similarstructures. Connectors are preferably formed from polar materials, whichare those materials whose polymers have electrons that are notsymmetrically distributed resulting in polymers having slightly positivesections and slightly negative sections. Exemplary polar materialsinclude but are not limited to poly(methyl methacrylate) (PMMA), styrenemaleic anhydride (SMA), polycarbonate (PC), and methylmethacrylate-acrylonitrile-butadiene-styrene (MABS).

An additive is a component added to a formulation which is not reactivewithin the formulation.

Principles and embodiments of the present invention relate generally tomedical devices and components used therein made from a base polymericformulation to which an additive comprising a polyethylene-poly(ethyleneoxide) amphiphilic graft copolymer (PE-g-PEO) is added via melt processbut can be incorporated via other mechanisms such dissolving in acompatible solvent. Methods of making and using these medical devicesand components are also provided herein.

Embodiments of the present invention provide benefits over the priorart. For example, the disclosed invention here is a clean system in thatthere are no reactive agents involved in the process, which eliminatesany concerns of un-reacted agents or residuals, especially for medicalapplications. In addition, the traditional solvent bonding processremains the same in that no further step is needed, such as a step ofapplying adhesives, either solvent based adhesive or bulk adhesive.Further, low amounts of additive achieve enhanced bonding. That is, thecopolymer additive is present in the base polymeric formulation in anamount in the range of about 0.01 to about 5.0% by weight of the basepolymeric formulation of the medical device component (e.g., tubing),which is not expected to have any impact on the component's finalproperties or the process to make the components. The PE-g-PEO copolymerhas been designed to have an extremely hydrophobic segment PE and anextremely hydrophilic segment PEO. The PE-g-PEO copolymer enhanced theinterfacial bonding strength between PE and a second polymer like PMMA,SMA, PC, and MABS at a loading of 0.5 wt.-%.

PE-g-PEO graft copolymers have two kinds of segments. The PE segmentsare miscible with a polyolefin such as polyethylene, and the PEOsegments are miscible/compatible with second materials such as PMMA,SMA, PC, or MABS. When PE-g-PEO is melt blended with a polyolefin suchas polyethylene, due to the hydrophilicity of the PEO segment, the graftcopolymers tend to surge to the polymer surface and remain there,although at a low concentration or loading (for example, about 5 wt.-%or less, or about 1 wt.-% or less, or even about 0.5 wt.-% or less).This differentiates itself from other compatibilizer system. Whensolvent bonding polyolefin (containing PE-g-PEO copolymers) with asecond material, the PE segments stay in the polyethylene side, whilethe PEO segments entangle, or adhere/interact, with the second material,PMMA, SMA, PC, or MABS. The PE-PEO graft copolymers work as a chemicalbridge connecting the otherwise immiscible polyethylene/second materialsand improve the interfacial bonding strength.

Typically, reactive blending/compatibilization is preferred due to itssuperiority in enhancing mechanical performance. For pre-madecopolymers, it would require minimum 5-10% loading by weight, in orderto achieve compatibilization or mechanical performance improvement. Forthe PE-g-PEO system, an amount of about 5 wt.-% or less of the copolymerachieves significant increase on interfacial bonding strength, which isunexpected. Without intended to be bound by theory, this can beexplained due to the fact that polyethylene (PE) and/or polypropylene(PP) present in tubing material has extremely good miscibility with PEsegments of the additive and the same time it is immiscible with PEOsegment that causes separation of PEO segment from the dissimilarpolymer matrix to the surface.

General Procedure for Synthesis of Pe-G-Peo & Preparation of Blend withBase Polymer Formulation

Polyethylene-poly(ethylene oxide) amphiphilic graft copolymers(PE-g-PEO) are additives for the base polymeric formulations ofcomponents of medical devices. These copolymers are discussed in U.S.Pat. No. 9,150,674 to common assignee, which is incorporated herein byreference. The process to make amphiphilic graft copolymers involvesgrafting poly(ethylene oxide) onto an ethylene vinyl acetate (EVA)platform using oxo-anion ring-opening polymerization chemistry.Polyethylene based graft copolymers are prepared starting frompoly(ethylene-co-vinyl acetate). The amphiphilic character will resultfrom the incorporation of hydrophilic poly(ethyleneoxide) (PEO)side-chains.

A process for preparing amphiphilic polyethylene-based copolymerscomprises obtaining an ethylene vinyl acetate copolymer having between2-40 weight percent of vinyl acetate; reacting the ethylene vinylacetate copolymer with potassium methoxide to prepare a mixture ofpolymeric potassium alkoxide and methyl acetate co-product; performingdistillation on the a mixture of polymeric potassium alkoxide and methylacetate co-product to remove the methyl acetate co-product; performingethylene oxide ring-opening polymerization on the polymeric potassiumalkoxide; removing aliquots during the ethylene oxide ring-openingpolymerization to allow for systemic variation in degree ofpolymerization of ethylene oxide side chains; and collecting anamphiphilic polyethylene based graft co-polymer.

An exemplary PE-g-PEO copolymer is shown according to Formula (I).

wherein R is hydrogen, alkyl, substituted alkyl, vinylic substitutedalkyl, hydrocarbyl, substituted hydrocarbyl, or vinylic substitutedhydrocarbyl group; the molar value of m is in the range from 2 to 40mole percent; the molar value of n is in the range from 60 to 98 molepercent; and p is in the range from 5 to 500 ethylene oxide units.Reference to “n” is with respect to ethylene units, “m” is to graftedPEO units, and “p” is to ethylene oxide units of the grafted chain.

The molar percentage value of m may be in the range of from 10 to 40mole percent. The molar percentage value of n may be in the range offrom 60 to 90 mole percent. The molar percentage value of p may be inthe range of from 5 to 400.

In one or more embodiments, the ethylene vinyl acetate copolymer has amelt index from 0.3 to 500 dg/min.

In one or more embodiments, the ethylene oxide ring-openingpolymerization is performed at a reaction temperature in the range of−20 to 100° C. In a specific embodiment, the ethylene oxide ring-openingpolymerization is performed at a reaction temperature of greater than30° C. In another specific embodiment, the ethylene oxide ring-openingpolymerization is performed at a reaction temperature of 60° C.

The ethylene oxide ring-opening polymerization may be performed underalkaline conditions. The ethylene oxide ring-opening polymerization maybe performed using 1,3 propane sultone.

In one or more embodiments, the amphiphilic polyethylene based graftco-polymer has a dispersity index in the range of 2 to 10, or even 1.05to 1.25.

Exemplary PE-g-PEO copolymer compositions are listed in Table 1.

TABLE 1 Exemplary PE-g-PEO copolymers Average —CH₂—CH₂— Interval NumbersAverage EO Nomenclature (Brush Density) Units in Brush (PE-XXX-g-PEO-z)(n) (p) PE-360-g-PEO-7 (PE1-g-PEO) 14 98 PE-460-g-PEO-4 (PE2-g-PEO) 17.472 PE-660-g-PEO-3.5 (PE3-g-PEO) 25 89 PE-760-g-PEO-0.25 36 9PE-760-g-PEO-1 36 36 PE-760-g-PEO-4 36 145 PE-760-g-PEO-8 36 280

Addition of the polyethylene-poly(ethylene oxide) amphiphilic graftcopolymer (PE-g-PEO) to the base polymeric formulation is done via meltprocessing. The term “melt processing” is used to mean any process inwhich polymers, such as the polyolefin, are melted or softened. Meltprocessing includes extrusion, pelletization, film blowing or casting,thermoforming, compounding in polymer melt form, fiber spinning, orother melt processes.

Any equipment suitable for a melt processing can be used as long as itprovides sufficient mixing and temperature control. For instance, acontinuous polymer processing system such as an extruder, a staticpolymer mixing device such as a Brabender blender, or a semi-continuouspolymer processing system, such as a BANBURY mixer, can be used. Theterm “extruder” includes any machine for polyolefin and TPE extrusion.For instance, the term includes machines that can extrude material inthe form of powder or pellets, sheets, fibers, or other desired shapesand/or profiles. Generally, an extruder operates by feeding materialthrough the feed throat (an opening near the rear of the barrel) whichcomes into contact with one or more screws. The rotating screw(s) forcesthe polyolefin forward into one or more heated barrels (e.g., there maybe one screw per barrel). In many processes, a heating profile can beset for the barrel in which three or more independentproportional-integral-derivative controller (PID)-controlled heaterzones can gradually increase the temperature of the barrel from the rear(where the plastic enters) to the front. When a melt extrusion is used,the mixing can take place during the melt extrusion step. The heatproduced during the extrusion step provides the energy necessary for themixing between different components. A temperature at or above themelting temperature of the polymer may be maintained for a timesufficient to mix all the components. For instance, the mixing time maybe at least 5 seconds, at least 10 seconds, or at least 15 seconds.Typically, the mixing time is 15-90 seconds.

Suitable blending temperature during melt mixing of polyolefins or TPEwith an additive should be sufficient to melt or to soften the componentof the composition which has the highest melting or softening point. Thetemperature typically ranges from 60 to 300° C., for instance, from 100to 280° C., from 90 to 150° C. One skilled in the art understands that apolyolefin or TPE mixtures thereof typically melts or softs over atemperature range rather than sharply at one temperature. Thus, it maybe sufficient that the polyolefin be in a partially molten state. Themelting or softening temperature ranges can be approximated from thedifferential scanning calorimeter (DSC) curve of the polyolefin ormixtures thereof.

TABLE 2 Exemplary Formulations (with the proviso that the ingredientstotal 100%). A B C Blend Ingredient by weight by weight by weight BasePolymeric   95-99.99%   95-99.99%   95-99.99% Formulation Polyethylene 50-100%  0-50%  0-50% Polypropylene  0-50%  50-100%  0-50%Ethylene-containing  0-50%  0-50%  50-100% Thermoplastic elastomer (TPE)Optional further  0-10%  0-10%  0-10% ingredients Polyethylene-poly0.01-5%   0.01-5%   0.01-5%   (ethylene oxide) amphiphilic graftcopolymer (PE-g-PEO) additive

In one or more embodiments, including Exemplary Formulations A, B, andC, the polyethylene-poly(ethylene oxide) amphiphilic graft copolymer(PE-g-PEO) additive may be present in amounts of about 0.01 to about5.0% by weight; about 0.1 to about 4.0% by weight; about 0.2 to about2.0% by weight; about 0.25 to about 0.75% by weight; or about 0.5 weight%.

Suitable linear low density polyethylene (LLDPE) for use in the processof the invention include copolymers of ethylene and α-olefins.Alpha-olefins include 1-butene, 1-hexene, and 1-octene, the like, andmixtures thereof. The density of LLDPE is preferably within the range ofabout 0.865 to about 0.925 g/cm³ (ASTM D792-13) and a melt mass flowrate of less than 0.5 g/10 min to greater than 20 g/10min based on therequirements of the manufacturing process and end application (190°C./2.16 kg, ASTM D1238-13). LLDPE is commercially available, forinstance Dowlex™ 2045.01 G LLDPE from Dow Chemical Company. SuitableLLDPE can be produced by a Ziegler-Natta, single-site, or any otherolefin polymerization catalysts.

Suitable polyethylene-polypropylene co-polymers may include—reactorgrade or melt blended mixtures of the polypropylene and polyethylenepolyolefins with or without polyolefin elastomers (final formulationcontaining from but not limited to about 10 wt.-% up to about 80 wt.-%ethylene and/or propylene monomeric units). The term “blend” or “polymerblend” generally refers to a mixture of two or more components. Such ablend may or may not be miscible, and may or may not be phase separated.

Suitable polyolefins include those prepared from linear or branchedolefins having 2 to 20 carbon atoms, 2 to 16 carbon atoms, or 2 to 12carbon atoms. Typically, the olefin used to prepare the polyolefin isα-olefin. Exemplary linear or branched α-olefins includes, but are notlimited to, ethylene, propylene, 1-butene, 2-butene, 1-pentene,3-methyl-1-butene, 4-methyl-1-pentene, 3-methyl-1-pentene, 1-hexene,3,5,5-trimethyl-1-hexene, 4,6-dimethyl-1-heptene, 1-octene, 1-decene,1-undecene, 1-dodecene, 1-tetradecene, 1-hexadecene, 1-octadecene, and1-eicocene. These olefins may contain one or more heteroatoms such as anoxygen, nitrogen, or silicon. The term “polyolefin” generally embraces ahomopolymer prepared from a single type of olefin monomer as well as acopolymer prepared from two or more olefin monomers. A specificpolyolefin referred to herein shall mean polymers comprising greaterthan 50% by weight of units derived from that specific olefin monomer,including homopolymers of that specific olefin or copolymers containingunits derived from that specific olefin monomer and one or more othertypes of olefin comonomers. The polyolefin used herein can be acopolymer wherein the comonomer(s) is/are randomly distributed along thepolymer chain, a periodic copolymer, an alternating copolymer, or ablock copolymer comprising two or more homopolymer blocks linked bycovalent bonds. Typical polyolefins include polyethylene, polypropylene,a copolymer of polyethylene and polypropylene, and a polymer blendcontaining polyethylene, polypropylene, and/or a copolymer ofpolyethylene and polypropylene. Polyolefin can also be an ethylene richimpact copolymer (may contain ethylene comonomer at the amount of atleast 10 wt.-%; and up to 40 wt.-%), i.e., a heterophasic polyolefincopolymer where one polyolefin is the continuous phase and anelastomeric phase is uniformly dispersed therein. This would include,for instance, a heterophasic polypropylene copolymer where polypropyleneis the continuous phase and an elastomeric phase is uniformly dispersedtherein. The impact copolymer results from an in-reactor process ratherthan physical blending. The polyolefins mentioned above can be made byconventional Ziegler/Natta catalyst-systems or by single-sitecatalyst-systems.

Suitable polyolefin elastomers for use in the process of the inventioninclude ethylene-propylene rubber (EPR), ethylene-propylene-dienemonomer rubber (EPDM), the like, and mixtures thereof. As used herein,the term “elastomer” refers to products having rubber-like propertiesand little or no crystallinity. Preferably, the polyolefin elastomerscontain from about 10 wt.-% up to about 80 wt.-% ethylene monomericunits. Illustrative polyolefin elastomers which are commerciallyavailable include Lanxess Corporation's BUNA EP T 2070 (22 MooneyML(1+4) 125° C., 68% ethylene, and 32% propylene); BUNA EP T 2370 (16Mooney, 3% ethylidene norbornene, 72% ethylene, and 25% propylene); BUNAEP T 2460 (21 Mooney, 4% ethylidene norbornene, 62% ethylene, and 34%propylene); ExxonMobil Chemical's VISTALON 707 (72% ethylene, 28%propylene, and 22.5 Mooney); VISTALON 722 (72% ethylene, 28% propylene,and 16 Mooney); and VISTALON 828 (60% ethylene, 40% propylene, and 51Mooney). Suitable EP elastomers available from commercial sources alsoinclude ExxonMobil Chemical's VISTAMAXX series of elastomers,particularly VISTAMAXX grades 6100, 1100, and 3000. These materials areethylene-propylene elastomers of 16, 15, and 11 wt.-% ethylene content,respectively, and a Tg of about −20 to −30° C. VISTAMAXX 6100, 1100, and3000, respectively, have a melt flow rate of 3, 4, and 7 g/10 min at230° C.; a density of 0.858, 0.862, and 0.871 g/cm³; and a 200 g Vicatsoftening point of 48, 47, and 64° C. Other suitable elastomers includeDow Chemical's VERSIFY propylene-ethylene copolymers, particularlygrades DP3200.01, DP3300.01, and DP3400.01, which have nominal ethylenecontents of 9, 12 and 15 wt.-%, respectively, and corresponding nominalpropylene contents of 91, 88, and 85 wt.-%, respectively. These gradeshave a melt flow rate of 8 g/10 min at 230° C.; a density of 0.876,0.866, and 0.858 g/cm³, respectively; a Vicat softening point of 60, 29,and <20° C., respectively; and a Tg of −25, −28, and −31° C.,respectively.

Preferably, the polyolefin elastomers contain from but not limited toabout 10 wt.-% up to about 80 wt.-% ethylene monomeric units. The term“thermoplastic elastomer” (TPE) in general defines blends of polyolefinsand rubbers in which blends of the rubber phase is not cured, i.e., socalled thermoplastic olefins (TPO), blends of polyolefins and rubbers inwhich blends of the rubber phase has been partially or fully cured by avulcanization process to form thermoplastic vulcanizates (TPV), orunvulcanized block-copolymers or blends thereof. Non-polar thermoplasticelastomer may made from a thermoplastic polyolefin homopolymer orcopolymer, and an olefinic rubber which is fully crosslinked, partiallycrosslinked or not crosslinked, and optionally commonly used additives;as well as a block-copolymer of styrene/conjugated diene/styrene and/orits fully or partially hydrogenated derivative.

Polyolefins suitable for use in TPE composition include thermoplastic,crystalline polyolefin homopolymers and copolymers. They are desirablyprepared from monoolefin monomers having but not limited to 2 to 7carbon atoms, such as ethylene, propylene, 1-butene, isobutylene,1-pentene, 1-hexene, 1-octene, 3-methyl-1-pentene, 4-methyl-1-pentene,5-methyl-1-hexene, mixtures thereof and copolymers thereof with(meth)acrylates and/or vinyl acetates. The polyolefins which can be usedin TPE formulations can be a high, low, linear-low, very low-densitypolyethylenes and copolymers of ethylene with (meth)acrylates and/orvinyl acetates. Polyolefins can be made by conventional Ziegler/Nattacatalyst-systems or by single-site catalyst-systems, or other polyolefincatalyst technology in combination with various process technologies andsolutions.

Suitable olefinic rubbers of the monoolefin copolymer rubbers comprisenon-polar, rubbery copolymers of two or more α-monoolefins, preferablycopolymerized with at least one polyene, usually a diene. Saturatedmonoolefin copolymer rubber, for example ethylene-propylene copolymerrubber (EPM) can be used. However, unsaturated monoolefin rubber such asEPDM rubber is more suitable. EPDM is a terpolymer of ethylene,propylene and a non-conjugated diene. Satisfactory non-conjugated dienesinclude 5-ethylidene-2-norbomene (ENB); 1,4-hexadiene;5-methylene-2-norbomene (MNB); 1,6-octadiene; 5-methyl-1,4-hexadiene;3,7-dimethyl-1,6-octadiene; 1,3 -cyclopentadiene; 1,4-cyclohexadiene;dicyclopentadiene (DCPD) and vinyl norbomene (VNB). Butyl rubbers arealso used in TPE formulation. The term “butyl rubber” includescopolymers of an isoolefin and a conjugated monoolefin, terpolymers ofan isoolefin with or without a conjugated monoolefin, divinyl aromaticmonomers and the halogenated derivatives of such copolymers andterpolymers. Another suitable copolymer within the olefinic rubber is acopolymer of a C₄₋₇ isomonoolefin, and a para-alkylstyrene. A furtherolefinic rubber used in TPE is natural rubber. The main constituent ofnatural rubber is the linear polymer cis-1,4-polyisoprene. Furthermorepolybutadiene rubber and styrene-butadiene-copolymer rubbers can also beused. Blends of any of the above olefinic rubbers can be employed,rather than a single olefinic rubber. Further suitable rubbers arenitrite rubbers. Examples of the nitrile group-containing rubber includea copolymer rubber comprising an ethylenically unsaturated nitrilecompound and a conjugated diene. Further, the copolymer rubber may beone in which the conjugated diene units of the copolymer rubber arehydrogenated. Specific examples of the ethylenically unsaturated nitrilecompound include acrylonitrile, α-chloroacrylonitrile,α-fluoroacrylonitrile and methacrylonitrile. Among them, acrylonitrileis particularly preferable. Other suitable rubbers are based onpolychlorinated butadienes such as polychloroprene rubber. These rubbersare commercially available under the trade names Neoprene® andBayprene®.

A commercially available thermoplastic elastomer (TPE) that showed somebenefits with the addition of PE-g-PEO is one formulated withoutplasticizers having a nominal density of 0.888 g/cm³ (ASTM D792-13) anda nominal composition of: 33.0 mol % propylene, 24.8 mol % ethylene, and42.2 mol % butylene.

Base polymeric materials with PE-g-PEO additive prepared with accordingto the process of the invention may be formed into useful articles bystandard forming methods known in the art, e.g., by blown filmextrusion, cast film extrusion, injection or blow molding, pelletizing,foaming, thermoforming, compounding in polymer melt form, or fiberspinning. For example, any technique discussed above in the embodimentsdescribing the melt processes can be used to prepare modified polymer,thereby forming various useful articles, depending on the type of meltprocessing technique used. For instance, blend may be used in makingfilms, such as blown or cast films. The techniques of blown filmextrusion and cast film are known to one skilled in the art in the areaof production of thin plastic films. Polymers with PE-g-PEO additive mayalso be used in coextruded films. The formation of coextruded blownfilms is known to one skilled in the art. The term “coextrusion” refersto the process of extruding two or more materials through a single diewith two or more orifices arranged such that the extrudates mergedtogether into a laminar structure, for instance, before chilling orquenching.

Turning to FIG. 1, a portion of an intravenous (IV) infusion kitcomprising tubing, an IV injection port, and connection is illustrated.A patient is connected to an IV source by means of an intravenous (IV)infusion kit. The kit comprises a length of tubing having connectors onthe ends and one or more injection sites or ports. The injection sitesor ports enable the injection of additional medications or the like viaa syringe or other IV source. The exemplary kit, as illustrated,comprises a needle 12 for insertion into a patient connected to tubing14 having a Y-site (connector) 16, and a tubing branch 18 for connectionto a source of IV fluid (not shown). The Y-site includes a conventionalIV injection site or port comprising an elastic plug and cap combination20 of Neoprene or the like on or over the end of a portion of theY-tube. The connection of an additional IV source for the injection of afluid is accomplished by inserting a conventional needle 22 through thesite or port 20 into the underlying tube. Embodiments of the presentinvention include tubing 14 being formed from a base polymericformulation comprising a polyolefin (e.g., polyethylene orpolypropylene) or a thermoplastic elastomer (TPE) to which is added anadditive comprising a polyethylene-poly(ethylene oxide) amphiphilicgraft copolymer (PE-g-PEO). The Y-site (connector) 16 may be formed froma material selected from the group consisting of: poly(methylmethacrylate) (PMMA), styrene maleic anhydride (SMA), polycarbonate(PC), and methyl methacrylate-acrylonitrile-butadiene-styrene (MABS).The tubing 14 is solvent-bonded to the Y-site (connector) 16.

General Procedure for Solvent Bonding

The solvent for treating outer surface of the tube is typically selectedfrom one or more hydrocarbons, such as cyclohexanone, cyclohexane,hexane, xylene, toluene, tetrahydrofuran (THF), ethyl acetate (EA) andmethyl ethyl ketone (MEK). Solvent treatment typically comprisesapplying the solvent to surface of the end portion of tube prior toinserting the end portion into the axial passage of the tubular body ofthe connector.

Solvent bonding is a method that allows two or more materials to bebonded together without the use of an adhesive. For example, Material“A” is a first component, such as tubing, that needs to be permanentlyaffixed (or bonded) to Material “B”, which may be a connector. BothMaterials “A” and “B” are dipped into a solvent that is suitable forprocessing of medical devices. The materials are then overlapped andsecured (e.g., by clamping) to form a bond area. The materials are keptin contact with each other for a time suitable to allow the overlappedarea to cure and form a bond.

Solvents suitable for assembling medical devices include but are notlimited to: cyclohexanone, methylene chloride, methyl ethyl ketone(MEK), tetrahydrofuran, acetone, 1, 2-dichloroethane, methyl benzene,tetrahydrofuran and blends of the solvents (50/50% methylenechloride/cyclohexanone, 50/50% or 80/20% MEK/cyclohexanone); bondingsolvent can be further loaded up to 25% by weight with the parentplastic or component of base formulation material (of the tube orconnector) to increase viscosity.

Embodiments

Various embodiments are listed below. It will be understood that theembodiments listed below may be combined with all aspects and otherembodiments in accordance with the scope of the invention.

Embodiment 1

A tubing for a medical device formed from a blend comprising: a basepolymeric formulation comprising at least a polymer or co-polymer ofethylene or propylene and excluding free poly(ethylene oxide); and anadditive comprising a polyethylene-poly(ethylene oxide) amphiphilicgraft copolymer (PE-g-PEO); the PE-g-PEO being present in the blend inan amount in the range of about 0.01 to about 5.0% by weight of theblend.

Embodiment 2

The tubing of embodiment 1, wherein the PE-g-PEO is according to Formula(I):

wherein R is hydrogen, alkyl, substituted alkyl, vinylic substitutedalkyl, hydrocarbyl, substituted hydrocarbyl, or vinylic substitutedhydrocarbyl group; the molar value of m is in the range from 2 to 40mole percent; the molar value of n is in the range from 60 to 98 molepercent; and p is in the range from 5 to 500 ethylene oxide units.

Embodiment 3

The tubing of one of embodiments 1 to 2, wherein the base polymericformulation comprises polyethylene, polypropylene, apolyethylene-polypropylene co-polymer, a polyethylene- and/orpolypropylene-containing thermoplastic elastomer (TPE), or combinationsthereof.

Embodiment 4

The tubing of embodiment 3, wherein the base polymeric formulationcomprises a co-polymer of polyethylene and polypropylene.

Embodiment 5. The tubing of embodiment 3, wherein thepolyethylene-and/or polypropylene-containing thermoplastic elastomer(TPE) comprises at least 60 mol % total polyethylene and/orpolypropylene.

Embodiment 6

The tubing of one of embodiments 1 to 5, wherein the PE-g-PEO is aproduct of ethylene oxide ring-opening polymerization of an ethylenevinyl acetate copolymer having from 10 to 40 weight percent of vinylacetate.

Embodiment 7

A medical device comprising: a tubing comprising a polymeric blendcomprising a base polymeric formulation comprising at least a polymer orco-polymer of ethylene or propylene and excluding free poly(ethyleneoxide), and an additive comprising a polyethylene-poly(ethylene oxide)amphiphilic graft copolymer (PE-g-PEO) according to Formula (I); whereinthe base polymeric formulation does not contain any free poly(ethyleneoxide) and the PE-g-PEO is present in the blend in an amount in therange of about 0.01 to about 5.0% by weight of the blend; and aconnector bonded to the tubing; wherein the PE-g-PEO is effective toenhance bonding of the tubing to a connector.

Embodiment 8

The medical device of embodiment 7, wherein the base polymericformulation comprises polyethylene, polypropylene, apolyethylene-polypropylene co-polymer, a polyethylene- and/orpolypropylene-containing thermoplastic elastomer (TPE), or combinationsthereof.

Embodiment 9

The medical device of one of embodiments 7 to 8, wherein the basepolymeric formulation comprises a co-polymer of polyethylene andpolypropylene.

Embodiment 10

The medical device of one of embodiments 7 to 8, wherein thepolyethylene-and/or polypropylene-containing thermoplastic elastomer(TPE) comprises at least 60 mol % polyethylene and/or polypropylene.

Embodiment 11

The medical device of any of embodiments 7 to 10, wherein the PE-g-PEOis a product of ethylene oxide ring-opening polymerization of anethylene vinyl acetate copolymer having from 10 to 40 weight percent ofvinyl acetate.

Embodiment 12

The medical device of one of embodiments 7 to 11, wherein the connectorcomprises a polar material.

Embodiment 13

The medical device of embodiment 12, wherein the polar material selectedfrom the group consisting of: poly(methyl methacrylate) (PMMA), styrenemaleic anhydride (SMA), polycarbonate (PC), and methylmethacrylate-acrylonitrile-butadiene-styrene (MABS).

Embodiment 14

The medical device of one of embodiments 7 to 13, wherein the connectoris solvent-bonded to the tubing.

Embodiment 15

A method of making a medical device comprising: obtaining apolyethylene-poly(ethylene oxide) amphiphilic graft copolymer(PE-g-PEO); combining the PE-g-PEO with a base polymeric formulationcomprising at least a polymer or co-polymer of ethylene or propylene andexcluding free poly(ethylene oxide) to form a blend, the PE-g-PEO beingpresent in the blend in an amount in the range of about 0.01 to about5.0% by weight of the blend; forming a tubing from the blend; bondingthe tubing to a connector in the presence of a solvent to form themedical device; wherein the PE-g-PEO is effective to enhance bonding ofthe tubing to a connector.

Embodiment 16

The method of embodiment 15, wherein ethylene oxide ring-openingpolymerization of an ethylene vinyl acetate copolymer having from 10 to40 weight percent of vinyl acetate is used to form the PE-g-PEO, whichis according to Formula (I).

Embodiment 17

The method of any one of embodiments 15 to 16, wherein the basepolymeric formulation comprises polyethylene, polypropylene, apolyethylene-polypropylene co-polymer, a polyethylene- and/orpolypropylene-containing thermoplastic elastomer (TPE), or combinationsthereof.

Embodiment 18

The method of one of embodiments 15 to 17, wherein the base polymericformulation comprises a co-polymer of polyethylene and polypropylene.

Embodiment 19

The method of one of embodiments 15 to 17, wherein thepolyethylene-and/or polypropylene-containing thermoplastic elastomer(TPE) comprises at least 60 mol % polyethylene and/or polypropylene.

Embodiment 20

For any embodiment 1 to 19, wherein the PE-g-PEO has a dispersity indexin the range of 2 to 10, or even 1.05 to 1.25.

Examples

PE-g-PEO graft copolymers tested herein were prepared according to themethods of U.S. Pat. No. 9,150,674. Specifically, polyethylene basedgraft copolymers were prepared from a poly(ethylene-co-vinyl acetate)starting material. Controlled ring-opening polymerization was used tograft polymer side chains of ethylene oxide onto the polyethylenebackbone to prepare polyethylene-graft-poly(ethylene oxide) (PE-g-PEO)copolymers having functionalized side groups. Incorporation ofhydrophilic poly(ethylene oxide) (PEO) side-chains onto the polyethylenebackbone resulted a copolymer with desired amphiphilic characteristics.

More specifically, the amphiphilic graft copolymers of the presentinvention were prepared in a two-step synthetic sequence. First, ahydrolysis reaction was performed on the EVA platform whereby theacetate units were removed to produce ethylene vinyl alcohol copolymers(EVOH) and a methyl acetate co-product. The acetate units were beremoved by reaction with potassium methoxide and the co-product methylacetate will be removed by distillation. The resultant polymericpotassium alkoxide was then used to initiate ethylene oxide ring-openingpolymerization (ROP). In the second step of the process, oxo-anionpolymerization was performed on the copolymers of ethylene and vinylacetate to produce polyethylene based graft-copolymers.

Example 1 Comparative

A first base polymer formulation based on a linear low densitypolyethylene (LLDPE) was prepared from Dowlex™ 2045.01 G only. A 4″×4″compression molded sample was prepared from the base polymer formulationat 155° C.

Example 2

A PE-g-PEO graft copolymer was prepared as PE-760-g-PEO-8, where 760 isan indication of the average distance between side-chains and 8 is theaverage length of the PEO side-chains. PE-760-g-PEO-8 graft copolymerwas added to the first base polymer formulation of Example 1 to form ablend, the graft copolymer being present in amounts of 0.5 wt.-%, 1.0%,2.5%, and 5.0% by weight of the blend. Exemplary components of medicaldevices were prepared by compression molding as set forth in Example 1.

Example 3

A PE-g-PEO graft copolymer was prepared as PE-760-g-PEO-4, where 760 isan indication of the average distance between side-chains and 4 is theaverage length of the PEO side-chains. PE-760-g-PEO-4 graft copolymerwas added to the first base polymer formulation of Example 1 to form ablend, the graft copolymer being present in amounts of 0.5 wt.-%, 1.0%,2.5%, and 5.0% by weight of the blend. Exemplary components of medicaldevices were prepared by compression molding as set forth in Example 1.

Example 4

PE-g-PEO graft copolymers were prepared as PE-760-g-PEO-z, where 760 isan indication of the average distance between side-chains and z, whichis the average length of the PEO side-chains, was varied. PE-760-g-PEO-zgraft copolymers were added to the first base polymer formulation ofExample 1 to form blends, the graft copolymer being present in aconstant amount of 0.5 wt.-% by weight of the blend. Values of “z” asvaried were: 0.25, 1, 4, and 8. Exemplary components of medical deviceswere prepared by compression molding as set forth in Example 1.

Example 5

PE-g-PEO graft copolymers were prepared as PE-XXX-g-PEO-z, where XXX isan indication of the average distance between side-chains and z, whichis the average length of the PEO side-chains, was varied to keep the PEOlength consistent. PE-XXX-g-PEO-z graft copolymers were added to thefirst base polymer formulation of Example 1 to form a blend, the graftcopolymers being present in a constant amount of 0.5 wt.-% by weight ofthe blend. Values of “XXX” & “z” as varied were: 360 & 7, 460 & 4, and660 & 3.5. As provided in Table 1, PE-360-g-PEO-7 may also be referredto as PE1-g-PEO, PE-460-g-PEO-4 may be referred to as PE2-g-PEO, andPE-660-g-PEO-3.5 may be referred to as PE3-g-PEO. Exemplary componentsof medical devices were prepared by compression molding as set forth inExample 1.

Example 6

A second base polymer formulation based on a commercially availablethermoplastic elastomer (TPE) only was prepared. The TPE was analyzed by13C-NMR and FTIR to contain 33.0 mol % propylene, 24.8 mol % ethylene,and 42.2 mol % butylene. A 4″×4″ compression molded sample was preparedfrom the base polymer formulation at 190° C.

A PE-g-PEO graft copolymer was prepared as PE-760-g-PEO-7, where 760 isan indication of the average distance between side-chains and 7 is theaverage length of the PEO side-chains. PE-760-g-PEO-7 graft copolymerwas added to the second base polymer formulation to form a blend, thegraft copolymer being present in amounts of 0.5 wt. %, 1.0%, 2.5%, and5.0% by weight of the blend. Exemplary components of medical deviceswere prepared by compression molding as set forth in Example 1.

Example 7

A PE-g-PEO graft copolymer was prepared as PE-760-g-PEO-4, where 760 isan indication of the average distance between side-chains and 4 is theaverage length of the PEO side-chains. PE-760-g-PEO-4 graft copolymerwas added to the second base polymer formulation of Example 6 to form ablend, the graft copolymer being present in amounts of 0.1%, 0.5 wt. %,1.0%, 2.5%, and 5.0% by weight of the blend. Exemplary components ofmedical devices were prepared by compression molding as set forth inExample 1.

Example 8

Effect of polyethylene (PE) content on bond strength of the TPEaccording to Examples 6-7 was determined. Varying amounts of PE wereadded to the TPE in combination with 0.5 wt. % PE760-g-PEO4. Exemplarycomponents of medical devices were prepared by compression molding asset forth in Example 1.

Example 9 Testing

Solvent Bonding Procedure. Each of the exemplary components of medicaldevices according to Examples 1-8 (Material “A”) was solvent bonded toan exemplary second component of a medical device (Material “B”) madefrom each of the following materials: poly(methyl methacrylate) (PMMA)(Plexiglas® SG10), styrene maleic anhydride (SMA) (Zylar® 960),polycarbonate (PC) (Makrolon® 2558), and methylmethacrylate-acrylonitrile-butadiene-styrene (MABS) (Terlux® 2802 HD).Materials “A” and “B” were both dipped into a cyclohexanone solvent andthen overlapped to create a 1 in² bond area. Samples were then clampedtogether and allowed to cure for 2 days.

Each system tested was one-factor-at-a-time (OFAT), with Material “A”the variable and Material “B” constant.

FIG. 2 provides a graph of bond strength (N) versus PE-g-PEOconcentration (weight %) for Comparative Example 1 (0%) and Example 2(0.5 wt.-%, 1.0%, 2.5%, and 5.0% by weight of the blend), which usedPE-760-g-PEO-8 as the additive to the base formulation. Bond strengthincreased as % PEO increased. The 0.5% loading showed significantimprovement over the comparative 0% example.

FIG. 3 provides a graph of bond strength (N) versus PE-g-PEOconcentration (weight %) for Comparative Example 1 (0%) and Example 3(0.5 wt.-%, 1.0%, 2.5%, and 5.0% by weight of the formulation), whichused PE-760-g-PEO-4 as the additive to the base formulation. Resultswith respect to all “B” materials are shown. Bond strength increased as% PEO increased. The 0.5% loading showed significant improvement overthe comparative 0% example.

FIG. 4 provides a graph of bond strength (N) towards PMMA material “B”versus PEO chain length (“z”) for Comparative Example 1 (PE only) andExample 4 (“z”: 0.25, 1, 4, and 8), which used PE-760-g-PEO-z as theadditive to the base formulation. The presence of PEO chains results inincreased bond strength. The highest bond strength occurred for z=1 andz=4.

FIG. 5 provides a graph of bond strength (N) towards SMA material “B”versus PEO chain length (“z”) for Comparative Example 1 (PE only) andExample 4 (“z”: 0.25, 1, 4, and 8), which used PE-760-g-PEO-z as theadditive to the base formulation. The presence of PEO chains results inincreased bond strength. The highest bond strength occurred for z=1 andz=4.

FIG. 6 provides a graph of bond strength (N) towards PC material “B”versus PEO chain length (“z”) for Comparative Example 1 (PE only) andExample 4 (“z”: 0.25, 1, 4, and 8), which used PE-760-g-PEO-z as theadditive to the base formulation. The presence of PEO chains results inincreased bond strength. The highest bond strength occurred for z=1 andz=4.

FIG. 7 provides a graph of bond strength (N) towards PC material “B”versus PEO chain length (“z”) for Comparative Example 1 (PE only) andExample 4 (“z”: 0.25, 1, 4, and 8), which used PE-760-g-PEO-z as theadditive to the base formulation. The presence of PEO chains results inincreased bond strength. The highest bond strength occurred for z=1 andz=4.

FIG. 8 provides a graph of bond strength (N) towards PMMA material “B”versus PE segment length for Comparative Example 1 (PE only) and Example5 (“PE1-g-PEO”, where “XXX” & “z” are 360 & 7, respectively; “PE2-g-PEO,where “XXX” & “z” are 460 & 4, respectively; and “PE3-g-PEO”, where“XXX” & “z” are 660 & 3.5, respectively), which used PE-XXX-g-PEO-z asthe additive to the base formulation. As in FIG. 4, the presence of PEOchains results in increased bond strength relative to ComparativeExample 1. The bond strength for the varying co-polymers were allstatistically the same. No significant trend was observed based on PEsegment length.

FIG. 9 provides a graph of bond strength (N) towards SMA material “B”versus PE segment length for Comparative Example 1 (PE only) and Example5 (“PE1-g-PEO”, where “XXX” & “z” are 360 & 7, respectively; “PE2-g-PEO,where “XXX” & “z” are 460 & 4, respectively; and “PE3-g-PEO”, where“XXX” & “z” are 660 & 3.5, respectively), which used PE-XXX-g-PEO-z asthe additive to the base formulation. The bond strength for the varyingco-polymers were all statistically the same. No significant trend wasobserved based on PE segment length.

FIG. 10 provides a graph of bond strength (N) towards PC material “B”versus PE segment length for Comparative Example 1 (PE only) and Example5 (“PE1-g-PEO”, where “XXX” & “z” are 360 & 7, respectively; “PE2-g-PEO,where “XXX” & “z” are 460 & 4, respectively; and “PE3-g-PEO”, where“XXX” & “z” are 660 & 3.5, respectively), which used PE-XXX-g-PEO-z asthe additive to the base formulation. The bond strength for thePE3-g-PEO and PE2-g-PEO were statistically the same. For PE1-g-PEO, bondstrength was significantly improved, for the co-polymer with the longestPE segment length.

FIG. 11 provides a graph of bond strength (N) towards MABS material “B”versus PE segment length for Comparative Example 1 (PE only) and Example5 (“PE1-g-PEO”, where “XXX” & “z” are 360 & 7, respectively; “PE2-g-PEO,where “XXX” & “z” are 460 & 4, respectively; and “PE3-g-PEO”, where“XXX” & “z” are 660 & 3.5, respectively), which used PE-XXX-g-PEO-z asthe additive to the base formulation. The bond strength for the varyingco-polymers were all statistically the same. No significant trend wasobserved based on PE segment length.

FIG. 12 is a graph of bond strength (N) versus PE-g-PEO concentration inbase formulation (weight %) for Example 6 (0%, 0.5%, 1.0%, 2.5%, and5.0% by weight), which used PE-760-g-PEO-7 as the additive to the baseformulation. For a loading of 0.5 wt. %, a modest increase in bondstrength was achieved by each of the four types of connector material.

FIG. 13 is a graph of bond strength (N) versus PE-g-PEO concentration inbase formulation (weight %) for Example 7 (0%, 0.5%, 1.0%, 2.5%, and5.0% by weight), which used PE-760-g-PEO-4 as the additive to the baseformulation. For PC at 1 wt.-% and PMMA at 1 and 2.5 wt.-%, there was anincrease in bond strength.

FIG. 14 provides a graph of bond strength (N) versus PE concentration inan exemplary TPE base formulation, which used 0.5 wt.-% ofPE-760-g-PEO-4 as the additive in the base formulation. From FIG. 14, itappears that a co-polymer PE-g-PEO is more effective when TPE ispolyethylene (PE) or polypropylene (PP) rich. After addition of 10% PEto TPE bonding strength of [TPE+0.5 wt. % PE-g-PEO] sample increased by23%.

Grafted copolymers show solvent bonding strength increase for PP and PErich TPE samples; suggesting that co-polymers are more effective in TPEscontaining at least 30-40 mol % or higher of each of propylene (C3)and/or ethylene (2) single component (TPE should be C3 or C2 rich). Fromthis, it appears that a preferred base polymeric formulation contains60-100 mol % (or 65-100 mol % or even 70-100 mol %) total ofpolyethylene and polypropylene.

Reference throughout this specification to “one embodiment,” “certainembodiments,” “one or more embodiments” or “an embodiment” means that aparticular feature, structure, material, or characteristic described inconnection with the embodiment is included in at least one embodiment ofthe invention. Thus, the appearances of the phrases such as “in one ormore embodiments,” “in certain embodiments,” “in one embodiment” or “inan embodiment” in various places throughout this specification are notnecessarily referring to the same embodiment of the invention.Furthermore, the particular features, structures, materials, orcharacteristics may be combined in any suitable manner in one or moreembodiments.

Although the invention herein has been described with reference toparticular embodiments, it is to be understood that these embodimentsare merely illustrative of the principles and applications of thepresent invention. It will be apparent to those skilled in the art thatvarious modifications and variations can be made to the method andapparatus of the present invention without departing from the spirit andscope of the invention. Thus, it is intended that the present inventioninclude modifications and variations that are within the scope of theappended claims and their equivalents.

What is claimed is:
 1. A tubing for a medical device formed from a blendcomprising: a base polymeric formulation comprising at least a polymeror co-polymer of ethylene or propylene and excluding free poly(ethyleneoxide); and an additive comprising a polyethylene-poly(ethylene oxide)amphiphilic graft copolymer (PE-g-PEO); the PE-g-PEO being present inthe blend in an amount in the range of about 0.01 to about 5.0% byweight of the blend.
 2. The tubing of claim 1, wherein the PE-g-PEO isaccording to Formula (I):

wherein R is hydrogen, alkyl, substituted alkyl, vinylic substitutedalkyl, hydrocarbyl, substituted hydrocarbyl, or vinylic substitutedhydrocarbyl group; the molar value of m is in the range from 2 to 40mole percent; the molar value of n is in the range from 60 to 98 molepercent; and p is in the range from 5 to 500 ethylene oxide units. 3.The tubing of claim 1, wherein the base polymeric formulation comprisespolyethylene, polypropylene, a polyethylene-polypropylene co-polymer, apolyethylene- and/or polypropylene-containing thermoplastic elastomer(TPE), or combinations thereof.
 4. The tubing of claim 3, wherein thebase polymeric formulation comprises a co-polymer of polyethylene andpolypropylene.
 5. The tubing of claim 3, wherein the polyethylene-and/orpolypropylene-containing thermoplastic elastomer (TPE) comprises atleast 60 mol % total polyethylene and/or polypropylene.
 6. The tubing ofclaim 1, wherein the PE-g-PEO is a product of ethylene oxidering-opening polymerization of an ethylene vinyl acetate copolymerhaving from 10 to 40 weight percent of vinyl acetate.
 7. The tubing ofclaim 1, wherein the PE-g-PEO has a dispersity index in the range of 2to
 10. 8. A medical device comprising: a tubing comprising a polymericblend comprising a base polymeric formulation comprising at least apolymer or co-polymer of ethylene or propylene and excluding freepoly(ethylene oxide), and an additive comprising apolyethylene-poly(ethylene oxide) amphiphilic graft copolymer (PE-g-PEO)according to Formula (I):

wherein R is hydrogen, alkyl, substituted alkyl, vinylic substitutedalkyl, hydrocarbyl, substituted hydrocarbyl, or vinylic substitutedhydrocarbyl group; the molar value of m is in the range from 2 to 40mole percent; the molar value of n is in the range from 60 to 98 molepercent; and p is in the range from 5 to 500 ethylene oxide units;wherein the PE-g-PEO is present in the blend in an amount in the rangeof about 0.01 to about 5.0% by weight of the blend; and a connectorbonded to the tubing; wherein the PE-g-PEO is effective to enhancebonding of the tubing to a connector.
 9. The medical device of claim 8,wherein the base polymeric formulation comprises polyethylene,polypropylene, a polyethylene-polypropylene co-polymer, a polyethylene-and/or polypropylene-containing thermoplastic elastomer (TPE), orcombinations thereof.
 10. The medical device of claim 8, wherein thebase polymeric formulation comprises a co-polymer of polyethylene andpolypropylene.
 11. The medical device of claim 8, wherein thepolyethylene-and/or polypropylene-containing thermoplastic elastomer(TPE) comprises at least 60 mol % polyethylene and/or polypropylene. 12.The medical device of claim 8, wherein the PE-g-PEO is a product ofethylene oxide ring-opening polymerization of an ethylene vinyl acetatecopolymer having from 10 to 40 weight percent of vinyl acetate.
 13. Themedical device of claim 8, wherein the connector comprises a polarmaterial.
 14. The medical device of claim 13, wherein the polar materialselected from the group consisting of: poly(methyl methacrylate) (PMMA),styrene maleic anhydride (SMA), polycarbonate (PC), and methylmethacrylate-acrylonitrile-butadiene-styrene (MABS).
 15. The medicaldevice of claim 8, wherein the connector is solvent-bonded to thetubing.
 16. A method of making a medical device comprising: obtaining apolyethylene-poly(ethylene oxide) amphiphilic graft copolymer(PE-g-PEO); combining the PE-g-PEO with a base polymeric formulationcomprising at least a polymer or co-polymer of ethylene or propylene andexcluding free poly(ethylene oxide) to form a blend, the PE-g-PEO beingpresent in the blend in an amount in the range of about 0.01 to about5.0% by weight of the blend; forming a tubing from the blend; andbonding the tubing to a connector in the presence of a solvent to formthe medical device; wherein the PE-g-PEO is effective to enhance bondingof the tubing to a connector.
 17. The method of claim 16, whereinethylene oxide ring-opening polymerization of an ethylene vinyl acetatecopolymer having from 10 to 40 weight percent of vinyl acetate is usedto form the PE-g-PEO, which is according to Formula (I):

wherein R is hydrogen, alkyl, substituted alkyl, vinylic substitutedalkyl, hydrocarbyl, substituted hydrocarbyl, or vinylic substitutedhydrocarbyl group; the molar value of m is in the range from 2 to 40mole percent; the molar value of n is in the range from 60 to 98 molepercent; and p is in the range from 5 to 500 ethylene oxide units. 18.The method of claim 16, wherein the base polymeric formulation comprisespolyethylene, polypropylene, a polyethylene-polypropylene co-polymer, apolyethylene- and/or polypropylene-containing thermoplastic elastomer(TPE), or combinations thereof.
 19. The method of claim 16, wherein thebase polymeric formulation comprises a co-polymer of polyethylene andpolypropylene.
 20. The method of claim 16, wherein thepolyethylene-and/or polypropylene-containing thermoplastic elastomer(TPE) comprises at least 60 mol % polyethylene and/or polypropylene.